Numerous types of medical devices have been developed for implantation into patients' bodies. For example, it has become common practice for dentists to provide their patients with custom dental prosthesis and/or implants to replace non-functional or missing teeth. The replacement prosthesis and/or implants can be individually designed and manufactured for precise installation into specific pre-identified sites. It has become routine for patients with abnormal or irregular rates of heart contractions, to have pacemaker devices installed under their skin in the chest area or alternatively, in their abdomens. Patients with debilitating degenerative diseases affecting their joints and/or skeletal elements are now able to have a large measure of their quality of life restored by replacement of the afflicted structures with man-made artificial implants such as replacement hip components, knee joint components, shoulder components, and the like. Patients who've suffered extreme trauma resulting in severely fractured bones are often provided with fracture fixation plates, fixtures, pins, nails, intramedullary rods, and the like to hold fractured bone segments together during the healing process and/or to replace destroyed or missing skeletal segments. However, all of these types of implantable devices expose the patients to risk of post-installation infection along and/or about the outer surfaces of the devices serving as colonization sites. Particularly problematic is the establishment of infectious biofilms on the surfaces of implanted devices. More severe cases of infection often result in microbial penetration into the inner structural components of the implants requiring their removal and replacement.
Numerous strategies have been employed in attempts to prevent post-installation infections occurring on and about the surfaces the implanted medical devices. For example, flexible resilient silicone-based coatings with antimicrobial and/or anti-fungal additives have been developed for encasing the outer surfaces of medical implants at the time of implant manufacture. Such coatings are typically produced by first, dissolving a suitable silicone exemplified by methyltri-methoxy silanes, methyl tri-acetoxy silanes, tetratchlorosilanes, vinyl trimetho-ryl silanes, gamma-ureidopropyltrimethoxy silanes, and the like, in a suitable solvent exemplified by toluenes, hexanes, xylenes, tetrahydrofurans, cyclohexanones, and the like. Second, dissolving an antimicrobial compound and/or an anti-fungal compound in a suitable solvent exemplified by n-methylpyrrolidinone, alkylesters of C1-12 carboxylic acids, and the like. Third, mixing together the silane solution and the antimicrobial and/or anti-fungal solution. Four, immersing medical implants into the mixed solutions followed by removal and air-drying of the encased implants, then baking at about 90° C. for up to one hour to set the coating and to completely evaporate the solvents. Such antibiotic-encased implants are purported to release the antimicrobial and/or anti-fungal compounds upon contact of the medical implant with tissues after implantation.
Another common approach has been to incorporate antimicrobial compounds and/or drugs into implants comprising polymeric materials, during their manufacture so that the antimicrobial compounds are eluted from the implants into the surrounding. These types of implants are generally referred to as drug-eluting implants. Some such implants are manufactured by dissolving the antimicrobial compounds into one or more solvents used for solubilising selected polymeric materials. The solubilised polymeric materials and antimicrobial compounds are mixed together and then poured or dispensed into forms wherein they solidify, and then are finished into the final implant. Other strategies involve first preparing an implant, then producing one or more recesses and/or crevices in selected locations on the outer surface, and then filling with recesses and/or crevices with a drug delivery matrix that this allowed to at least semi-harden. The drugs are then eluted from the matrix over a period of time. In some implant combinations, for example a “ball” and “socket” combination for a complete hip replacement or a total knee replacement package comprising a femoral component, a tibial tray, a tibial insert, and a patellar component, the drug delivery matrix may be incorporated into weight-bearing surfaces of one or more components so that the drugs are released by frictional forces created when two or more implant components rub against each other during their normal articulating functions. Other implant drug-eluting strategies have reservoirs cast into the implants' interior structure. The reservoirs are filled with drug solutions prior to installation of an implant into a patient. Some implants are configured to communicate and cooperate with external reservoirs containing drug solutions that are externally pumped into and/or about the implants on prophylactic schedules or alternatively, when an infection is detected. It is general practise to use antibiotic-loaded cements exemplified by PROSTALAC® (PROSTALAC is a registered trademark of Depuy Orthopaedic Inc., Warsaw, Ind., USA) and SIMPLEX® (SIMPLEX is a registered trademark of Howmedica Osteonics Corp., Mahwah, N.J., USA) for installation of orthopaedic implants. While these cements have considerable value for minimizing the occurrence of post-operative infections immediately after installation of orthopaedic implants, their long-term benefits are limited because the antibiotics tend to rapidly dissipate from the surfaces of the cements upon exposure to mammalian tissues.
There still remain numerous infection-susceptibility related problems with the implants commonly available and in general use. There are concerns that the efficacies of some antimicrobial compounds and/or drugs are altered or compromised by the solvents which are used for their dissolution and/or by solvents used for dissolution of polymeric materials used for casting implants. Furthermore, it is known that the efficacies of drug-eluting implants increasingly diminish over time and are limited by drug “loading” limitations by the implant manufacturing processes. Implants provided with drug-loaded recesses/crevices may provide protection from infections about the crevice sites for a period of time, but are quite susceptible to microbial colonization and biofilm formation on their surface areas at locations removed from the recesses/crevices. Compounding these problems, are the surgical challenges of removing the infected implants, abrading surrounding infected skeletal structures, excising surrounding infected tissues, and installing replacement implants.